Glioma is the most common malignant primary brain tumor and it will always recur. To date, various multimodal imaging including magnetic resonance imaging (MRI) and positron emission tomography computed tomography (PET/CT) was used to differentiate the diagnosis of true tumor recurrent (TuR) and treatment-related effects (TrE) in glioma patient but with no overall conclusion. In this study, SROC curve and Bayesian network meta-analysis will be used to conduct a comprehensive analysis of the results of different clinical reports, and assess the efficacy of multimodal imaging in difference TuR and TrE.To find more comprehensive information about the application of multimodal imaging in glioma patients, we searched the EMBASE, Pubmed, and Cochrane Central Register of Controlled Trials for relevant clinical trials. We also reviewed their reference lists to avoid omissions. QUADAS-2, RevMan software, Stata, and R software will be used.This study will provide reliable evidence for the efficacy of multimodal imaging in the differential diagnosis of TuR and TrE in glioma patients.We will evaluate the effectiveness of different and rank each imaging method in glioma patients to provide a decision-making reference on which method to choose for clinicians. Protocol registration number: CRD42020217861.Copyright © 2021 Elsevier B.V. All rights reserved.